Central synaptic impairment persists in sensory and motor neurons that regenerate their peripheral axonal projections after nerve injury. New findings obtained in this grant period suggest that these impairments modify feedback about muscle length and motor activity and cause significant dysfunction of spinal circuits responsible for coordinating muscle activity. This proposal has two objectives in studying the central mechanisms that limit recovery of movement following nerve repair: (1) locate deficits within and imbalances between selected spinal circuits and (2) manipulate activity of afferents in attempt to restore the usefulness of sensory feedback. Experiments designed to meet the specific aims described below all involve electrophysiological study in vivo of adult rats months after a selected few muscle nerves are severed and surgically repaired. The physiological studies proposed here will be coordinated with morphological studies in Project 2 in order to enable function-structure interpretations. Specific Aim 1 is motivated by findings obtained in this grant period which suggest the counterintuitive notion that inactivity of regenerated primary afferents promotes their recovery of synaptic transmission with motoneurons. Experiments will manipulate afferent activity in attempt to rescue central transmission of muscle-length feedback for those afferents which recover stretch sensitivity through peripheral regeneration. Specific Aim 2 focuses on the recovery of recurrent feedback from motoneurons which is shown by Projects 1 and 2 to be incomplete despite successful regeneration of peripheral motor axons. Resultant modification of the spinal circuit receiving recurrent feedback will be probed in detail to test sites of dysfunction. Specific Aim 3 will examine apparent imbalances in excitatory and inhibitory spinal circuits associated with dyscoordination of antagonist muscle activity. Meeting these aims will substantially advance this project's long-term goal of explaining the failure to regain normal central transmission from neurons that regenerate successfully in the periphery after nerve injury. These central impairments together with incomplete and misdirected regeneration in the periphery conspire to prevent nerve repair from restoring normal movement. By addressing the causes of deficits in purposeful movement, this project advances the mission of the NINDS to improve treatment of neurological disorders.